1. To evaluate the possible role of sodium channel in the neurotoxicity of the organochlorine insecticides in vivo in rats. p,p'-DDT and related agents act to hold the sodium channel open once opened and this effect is believed to be responsible for neurological effects of tremor and hyperexcitability in vivo. Tremor was almost completely blocked in rats pretreated with hydantoin, an anticonvulsant believed to block repetitive firing of nerves by interfacing with the inactivation gates of sodium. A similar antagonism was observed for permethrin, a Type I pyrethroid believed to have a mechanism equal to that of DDT. However, hydantoin increased the tremorigenic effects of chlordecone, an organochlorine whose mechanism has not been linked to the sodium channel. Our data are consistent with the hypothesis that in vivo neurotoxicity of some organochlorine insecticides is related to their effects on the sodium channel. 2. To characterize neurochemical effects of chlordecone on the hypothalamopituitary-adrenal axis. A single injection of a tremorigenic dose of chlordecone (75 mg/kg, i.p.) increased the levels of plasma and adrenal corticosterone and the plasma level of ACTH. The increase in the pituitary-adrenal activity is consistent with morphological observations which indicate that adrenal cortical cells and corticotrophs of the pituitary hypertrophy after chlordecone exposure. Pretreatment with phenoxybenzamine and pizotifen (a 5-HT receptor blocker) completely prevented chlordecone-elicited increase in plasma levels of ACTH and corticosterone suggesting that monoamine mechanisms within the hypothalamus may mediate the neuroendocrine effects of chlordecone on the pituitary-adrenal axis. This project will be terminated.